Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Medicine, and Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria.

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Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Department of Medicine, and Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: kawut@upenn.edu.

Abstract

BACKGROUND:

Six-minute walk distance (6MWD) and brain natriuretic peptide (BNP) levels at baseline and after initiation of treatment have been associated with survival in patients with pulmonary arterial hypertension. Our objective was to determine the individual and additive ability of pretreatment and posttreatment 6MWD and BNP to discriminate 2-year survival in patients with pulmonary arterial hypertension.

METHODS:

We included patients enrolled in two randomized clinical trials of ambrisentan who had 2-year follow-up (N 5 370). 6MWD and BNP were assessed before and after 12 weeks of treatment. Receiver operating characteristic curve analyses were performed to identify optimal cutoffs that defi ned subgroups with a high 2-year mortality. Classifi cation and regression tree analysis was used to determine the incremental prognostic value of combined assessments.

RESULTS:

6MWD at baseline and after 12 weeks of therapy were similarly discriminatory of 2-year survival (c-statistics 5 0.77 [95% CI 0.70-0.84] and 0.82 [95% CI 0.75-0.88], respectively), whereas change in 6MWD from baseline to week 12 was not discriminating. The same observation was true of BNP at baseline and after 12 weeks of therapy (c-statistics 5 0.68 [95% CI 0.60-0.76] and 0.74 [95% CI 0.66-0.82], respectively). After consideration of baseline 6MWD, there was no prognostic information added by the week 12 6MWD or BNP at either time point.

CONCLUSIONS:

6MWD and BNP values at baseline or week 12 identifi ed a population with an elevated risk of death at 2 years. A repeat assessment of 6MWD or BNP after 12 weeks of ambrisentan therapy did not provide additional prognostic information beyond that obtained from baseline values.

ROC curves for predicting risk of death at 2 years. A, Baseline and week 12 6MWD. B, Change in 6MWD. CFB = change from baseline; ROC = receiver operating characteristic. See legend for expansion of other abbreviations.